DMD is a fatal genetic disease that leads to muscle weakness and wasting, resulting in breathing or heart failure usually before the age of 30 in humans. The researchers at the University of Texas' Southwestern Medical Centre and Royal Veterinary College in London delivered CRISPR/Cas9 apparatus to the muscle cells of four dogs using a modified virus.
The DNA of muscle cells was edited to repair a mutation in the DMD gene, which codes for dystrophin, a protein vital for muscle function. The particular mutation targeted in this study affects about 13 percent of patients with DMD.
'I feel this procedure is extremely promising based on our preliminary findings, but more work is needed to ensure safety,' said Professor Eric Olson, who led the research team at the University of Texas.
As this was the first study of its kind in larger mammals, the researchers used a small number of animals – four dogs unable to make dystrophin – for a proof-of-concept study. Two of the dogs received an injection directly into a muscle in one of their back legs. Their levels of the dystrophin protein in the skeletal muscles (those used for locomotion) were measured six weeks later. In dogs that had the treatment, dystrophin levels were boosted to almost 60 percent of normal levels.
Then, another two dogs were given the treatment in an intravenous injection and measured after eight weeks. These dogs had very variable levels of dystrophin, from 3 percent to 90 percent of normal in their skeletal muscles. The intravenous injection also boosted dystrophin levels to 58 percent in the diaphragm and 92 percent in the heart muscles.
Professor Richard Piercy, a comparative neuromuscular disease researcher at the Royal Veterinary College, said: 'The ambition is to show that this is safe and effective in dogs and then move into human trials. If that works, then the treatment could also apply to pet dogs that we see in our clinics – and that's what we hope for here at the college, as it's our goal to make animals better.'
The study focused on one mutation in particular, but there are hopes that the technique can be used for different forms of DMD.
The researchers are now planning to conduct a longer study with more animals to assess the safety and effectiveness of the treatment. If those are successful, clinical trials in humans could pave the path towards a cure for DMD in the future.
However, noting the limitations of the small study, Dr Kate Adcock, director of research and innovation at Muscular Dystrophy UK, said: 'Although it seems to have largely boosted dystrophin production, which is key to tackling this condition, the team weren't looking to record improvements in function. This won't be a cure, but that shouldn't obscure that this is a key step forward in proving the CRISPR-Cas9 technology could work for [DMD].'